Angiopoietin-2 targeted therapy suppresses tumor cell invasion and the formation of metastasis in SCLC

Down to the present day, small cell lung cancer (SCLC) is considered as one of the deadliest cancer entities. Because of its early metastasis formation and multidrug resistance SCLC occupies a special place within cancer research. Regarding the lack of treatment for SCLC especially in progressed state it is vital to examine how certain signalling cascades contribute to the highly aggressive phenotype and migration potential of SCLC.

In a previous screening elevated CD29 expression was observed in liver metastasis. Therefore, by CRISPR knockout a CD29KO cell line was generated to test the characteristics on functional and cellular level. Tumour cells in liver metastasis were additionally found to downregulate MHCI. To examine the specific effects of an MHCI loss on the cancer cell and its effect on immune system interactions MHCI knockout was performed.

In vitro migration assays revealed that CD29KO leads to an abrogation of fibronectin and angiopoietin (ANG-2) stimulated migration. In vivo experiments showed that in contrast to the wild type CD29KO Clones lose their capacity to form liver metastases. The MHCIKO was found to produce a more aggressive, fast-growing phenotype. We found a decreased immune cell answer for example considering lower T-cell infiltration in the pleura.

Our study states the importance of the CD29-ANG-2 signalling axis during metastasis formation. CD29 is a potent driver of liver metastasis in SCLC which can be abrogated by knockout.